The history of our understanding and approach to cancer are at the center of CANCER: THE EMPEROR OF ALL MALADIES, a film directed by Barak Goodman and executive produced by Ken Burns. The documentary, which features the Cancer Center at CHOP, will air in three parts on March 30, 31 and April 1 at 9 …

CHOP Research was awarded more than $500,000 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support the CHOP Research Institute Summer Scholars Program (CRISSP).

Alexander Fiks, MD, MSCE, a faculty member at The Children’s Hospital of Philadelphia, commented about a study appearing in JAMA Pediatrics that described an approach to using health information technology to increase vaccination coverage.

Dr. Campbell led a recent Journal of Pediatric Orthopaedics study that showed VEPTR treatment improved Jeune syndrome (a severe form of TIS) patients’ survival to nearly 70 percent, compared to a 70 to 80 percent mortality rate without treatment. To learn more about this inspirational work, check out the video below, the first on CHOP Research’s new YouTube channel!

CVID affects one in 25,000 to one in 50,000 people worldwide, and they may start experiencing signs and symptoms of the disorder anytime between childhood and adulthood. Researchers suspect that mutations in the genes associated with CVID result in a shortage of antibodies that leaves the body vulnerable to infections from bacteria and viruses. Recurrent respiratory infections can lead to chronic lung disease, and patients also may have joint inflammation, stomach and bowel disorders, and a higher risk of cancers.

The study team performed an association analysis that focused on immune-related genes in a cohort of 360 CVID patients and 21,610 healthy controls. They compared regions of the genome using a genotyping chip specialized to search for gene variants previously implicated in autoimmune and inflammatory diseases.

The researchers found 11 single nucleotide polymorphisms (SNPs) associated with CVID on the 16p11.2 locus of chromosome 16. SNPs are changes in a single DNA building block (A,T, C, or G), compared to the more typical sequence in a certain stretch of DNA. Of particular interest, the study team found variants in the gene ITGAM, which carries codes for an integrin protein that regulates cellular contact and adhesion.

“This association is of high biological relevance because ITGAM plays an important role in normal immune responses,” said Hakon Hakonarson, MD, PhD, director of the CAG, who led the study team. “Other researchers have shown that mice in which this gene has been knocked out have immune deficiencies.”

The new findings may promote better understanding of ITGAM’s functional role and eventually lead to targeted therapies for patients with CVID. Dr. Hakonarson added that the research may have broader implications for other patients who do not have these novel gene variants because the integrin protein affects many important pathways in immune function.

“This discovery fits well with the ‘precision medicine’ concept that is currently in its infancy but represents the future of genomic medicine,” said Dr. Hakonarson, who is also on the faculty of Perelman School of Medicine at the University of Pennsylvania.

It is challenging for clinicians who are treating a patient with acne to accurately measure disease activity from visit to visit. Often, they must rely on personal memory and the patient’s perspective to determine if the skin problem is improving, which can be an imprecise and time-intensive process.

In the U.S., it is estimated that 60 million people have acne, and one-fourth will seek out medical services; however, pediatric dermatology services are particularly difficult for patients to access with referral wait periods that can exceed more than three months.

Albert Yan, MD, Section Chief of the Division of Dermatology at The Children’s Hospital of Philadelphia and associate professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and co-developers Elena Bernardis, PhD, and Jianbo Shi, PhD, are creating a software program using sophisticated computer vision algorithms that will expedite clinical visits for acne and allow physicians to spend more valuable time on patient education.

“We are excited about this project because of the great potential to streamline the efficiency of primary care management of this disease in a way that adheres to accepted evidence-based guidelines and reduces unnecessary referrals of less severe disease to specialists,” Dr. Yan said.

Including noting the “science of vaccines is clear” in a Jewish Exponent article, The Children’s Hospital of Philadelphia physician and Vaccine Education Center Director Paul A. Offit, MD, spoke to a number of media outlets about the recent measles outbreaks and the vaccine worries the outbreaks have induced. Dr. Offit is one of the most outspoken vaccine advocates in the country and co-creator of the rotavirus vaccine Rotateq.

“I think it’s a shame that what we have to be seeing in this country right now, which is measles coming back now with more than 100 cases, that we have to … suffer our bad choices by watching children suffer diseases which are preventable,” said Dr. Offit on CNN’s Erin Burnett Out Front. “I mean it’s always the children that suffer,” he added.

Measles is a highly contagious viral disease that results in an itchy rash. Between January 1 and February 27, 2015, 170 cases of measles were diagnosed in the District of Columbia and 17 states across the U.S., according to the CDC.

And according to additional CDC data, until recently measles had been on the decline, with the disease declared eliminated in the U.S. in 2000. However, outbreaks in 2014 and 2015 show a marked rise in the incidence of the disease.

In a press briefing about the measles outbreaks, the CDC’s Anne Schuchat, MD, director of the National Center of Immunization and Respiratory Diseases, said the “majority of the adults and children that are reported to us for which we have information did not get vaccinated or don’t know whether they have been vaccinated. This is not a problem with the measles vaccine not working. This is a problem of the measles vaccine not being used.”

Indeed, because measles is viral, there is no treatment for the disease, and the best protection is the measles, mumps, and rubella (MMR) vaccine. However, some parents have refused to give their children the MMR vaccine, fearing it could lead to autism.

The link between vaccines and autism dates to a retracted 1998 The Lancet paper by British physician Andrew Wakefield, MD. That now-debunked study started a series of vaccine safety concerns related to autism that were fueled by a well-organized anti-vaccine movement, vocal celebrities like Jenny McCarthy, and poorly researched media reports. Each concern put forth by the anti-vaccine movement — whether MMR vaccine carried risks, to mercury in vaccines, or whether children received too many vaccines — was studied scientifically and disproven. Nonetheless, the damage was done.

“Two fundamentalist Christian churches — Faith Tabernacle Congregation and First Century Gospel Church — were at the heart of the outbreak. Children had not been vaccinated, and when they became ill, their parents prayed instead of taking them to the hospital to receive the intravenous fluids or oxygen that could have saved the lives of those with the worst cases.”

Pregnancy can be a magical time for many women, but it also can be a sleepless one. New research by a sleep expert at The Children’s Hospital of Philadelphia shows that a high prevalence of a spectrum of sleep problems occurs across all months of pregnancy, and that napping during the day should be considered the norm for moms-to-be.

“Past studies only considered sleep and pregnancy at one point in time or trimester,” said the study’s author Jodi Mindell, PhD, a psychologist and associate director of the Sleep Center at CHOP. “We looked at what were the most common sleep issues by month of pregnancy, and now that we know that information, we can start developing interventions.”

Dr. Mindell collected data from an online questionnaire that 2,427 pregnant women accessed via a popular pregnancy website over a four-day period in April 2014. Upon analyzing the data, Dr. Mindell found that almost all the study participants reported that they frequently woke up at night throughout pregnancy. These sleep disruptions were due mainly to their increased need to urinate and difficulty finding a comfortable sleep position.

Overall, three out of four women reported having poor sleep quality, which could contribute to the lack of energy and increased fatigue most women experienced throughout pregnancy. Eighty percent of the study’s participants took naps during the day.

Pregnant women also reported a high prevalence of sleep disorders. One out of five women had symptoms of sleep-disordered breathing, such as snoring and sleep apnea. One out of four women had restless leg syndrome symptoms.

“What I was struck by was how sleep problems really do not change across pregnancy,” Dr. Mindell said. “There are some symptoms that change; for example, being uncomfortable increases by the time you are seven or eight months pregnant. But for sleep quality, we didn’t see any change at any point in time. There is no ‘second-trimester honeymoon’ that people always talk about. These data give the message that we need to take sleep issues seriously in pregnant women and not discount them by saying they’re short-lived or the baby’s coming.”

In fact, sleep problems during pregnancy may have lasting effects even after delivery, especially in terms of their association with post-partum depression, Dr. Mindell pointed out. She encouraged healthcare practitioners to ask every pregnant woman about her sleep during prenatal visits to screen for sleep disturbances and then consider nonpharmacologic solutions, if needed.

“One out of 10 women were taking a sleep medication in the past month, so it appears that women are treating themselves, and they may not be using the most appropriate treatment,” Dr. Mindell said. “That is concerning.”

The next step is for researchers to study safer ways to help women improve their sleep during pregnancy, Dr. Mindell said. For example, cognitive-behavioral therapy has been shown to alleviate insomnia, and it could teach pregnant women how to deal with worries about the baby or labor that may be keeping them awake.

The current study was published online in Sleep Medicine, and the project was supported by Johnson & Johnson Consumer & Personal ProductsWorldwide, a division of Johnson & Johnson Consumer Companies Inc.

A team of investigators from PolicyLab recently received an award from the William T. Grant Foundation to examine antipsychotic prescribing practices. Led by David Rubin, MD, MSCE, the co-director of PolicyLab, the researchers plan to study whether novel, narrative-informed guidelines that tell stories have a deeper impact on clinicians’ practices than standard guidelines.

Dr. Rubin and colleagues — including Zachary Meisel, MD, MPH, MSc, from the University of Pennsylvania’s Department of Emergency Medicine — plan to compare narrative-accompanied prescription guidelines with more traditional, “didactic” evidence-based prescription guidelines. Over the course of their project, Dr. Rubin and his team hope to determine whether guidelines that both involve a narrative component and give clinicians a voice have any effect on antipsychotic prescribing habits.

The study comes as concerns grow about the increasing rate of antipsychotic prescriptions for children. Antipsychotics are a class of medications used to treat mental and behavioral health disorders. Traditionally, antipsychotics, which act like powerful sedatives, have been prescribed only to children with major psychotic disorders such as schizophrenia, bipolar disorder, and autism. But these medications are increasingly being prescribed off-label to treat disruptive behaviors, a practice that lacks supporting data.

The use of antipsychotic medications among children has risen significantly over the past twenty years, largely because of their growing use to manage disruptive behaviors. Youth who are especially at-risk for increasing prescription of antipsychotic medications are Medicaid-enrolled children, for whom antipsychotic prescribing has grown at a rate far exceeding that for children who are privately insured.

Overall, some 25 percent of Medicaid-enrolled children receiving mental health treatment were prescribed antipsychotics by 2007, largely for less severe disorders like attention deficit hyperactivity disorder (ADHD). Particularly alarming, especially given their complex trauma histories, children in foster care are prescribed antipsychotic medications at a rate three times higher than children enrolled in Medicaid overall.

Another cause for concern is the growing practice of polypharmacy, the prescription of antipsychotic medications prescribed in combination with other mental health drugs. In a study published in the Journal of the American Academy of Child & Adolescent Psychology, Dr. Rubin and colleaguesfound that children were increasingly prescribed antipsychotic medications alongside other psychotropic medications, such as stimulants, at the same time.

The rise in antipsychotic prescriptions also points to a need for — and a lack of — non-pharmaceutical behavioral health treatment options for an at-risk population of children and youth. Only specialized behavioral health treatments can address the underlying trauma often driving disruptive behaviors.

A Powerful Story Will Stick

The study team plans to conduct their study in two parts. In its first phase, they will conduct semi-structured interviews with a sampling of Pennsylvania clinicians to elicit narratives from them. They will seek to interview between 30 and 50 clinicians across a range of specialties, with the goal of identifying key themes and constructs that influence clinicians’ prescribing habits.

By synthesizing data from the clinician interviews, the investigators will create sample narratives that use real events but redact confidential information. A focus group will help the investigators narrow these synthesized narratives down to three “core” narratives to be tested in the second phase of the research project.

“We know that stories can help patients — there are some excellent studies showing that stories which maximize concepts such as homophily (where the audience identifies with the storyteller) can move patients to engage in healthier behavior, including controlling their blood pressure and getting a cancer screening,” he writes. In addition, “stories can help researchers and clinicians translate evidence to policymakers in salient and coherent ways.”

In the study’s second phase, the researchers will test the effectiveness of the narrative-influenced guidelines. They plan to target psychiatrists, pediatricians, and family practitioners across Pennsylvania, whom they will break into three groups. One group, a control, will only receive standard recommendations, while the “low-dose” and “high-dose” arms of the study will receive one and three narratives, respectively. Medicaid claim data will be used to ascertain how effective each arm was.

To read more about this project, see this February issue of CHOP Research’s Bench to Bedside.

The VEPTR is the first device approved by the FDA to treat thoracic insufficiency syndrome (TIS), a rare congenital condition affecting children in which the thorax cannot support regular growth or breathing. By separating the ribs and helping to straighten the spine, the VEPTR is designed to give children’s lungs to grow, allowing them to breathe without the aid of ventilators.

Left untreated, TIS can be devastating. As children with TIS grow, the condition causes the chest become deformed, and children with TIS are often born with scoliosis, or curvature of the spine. TIS can lead to death due to respiratory insufficiency. However, since Dr. Campbell implanted the first VEPTR in 1989, the device — which as its name implies can be expanded as the child grows — has proven to be a lifesaver.

The founder and Director of Children’s Hospital’s Center for Thoracic Insufficiency Syndrome, Dr. Campbell is also a professor of Orthopaedic Surgery at the University of Pennsylvania’s Perelman School of Medicine. A highly accomplished pediatric orthopaedic surgeon, Dr. Campbell has been working to improve outcomes for TIS patients for more than 25 years.

Postoperative image after treatment with VEPTR.

A very rare disease, Jeune syndrome — or asphyxiating thoracic dystrophy — affects approximately 1 in 100,000 infants each year. A multisystem, congenital disorder, Jeune syndrome is characterized by distinctive narrow, bell-shaped chest, shortened limbs, and at times polydactylism. Those born with Jeune syndrome experience breathing problems, and can develop renal, hepatic, and cardiac issues. The chest hypoplasia caused by Jeune syndrome results in severe thoracic insufficiency syndrome.

In the Journal of Pediatric Orthopaedics paper, Dr. Campbell and colleagues describe the use of VEPTR to treat 24 patients with Jeune syndrome, at an average of 23 months of age. Of those, two were lost to follow-up, and 17 had a minimum of two years of follow-up examinations. In all, the survival rate of the 22 patients was 68 percent, with less dependence on ventilators.

“This study is, to our knowledge, the largest of the surgical treatment of Jeune syndrome with long-term follow-up, and we are especially excited that the survival rate after surgery was nearly 70 percent, compared to a 70 to 80 percent mortality rate for untreated Jeune syndrome patients, and most were weaned off their ventilators,” said Dr. Campbell.

In addition to the dramatic about-face in survival rate, the researchers also noted VEPTR treatment increased total chest diameter, thoracic spine height, and lumbar spine height. Assisted ventilation rating scores— which Dr. Campbell and his team used to measure pulmonary function — improved in many of the patients, with several who had been entirely dependent on a ventilator before surgery weaned off after treatment.

Dr. Campbell’s Journal of Pediatric Orthopaedics study is hardly the only promising research that makes use of the VEPTR. A search of PubMed reveals a host of VEPTR-related papers, including 27 since the beginning of 2013.

“New advances in surgery occur frequently, but only the test of time can show their true worth at long term follow-up,” Dr. Campbell added. “The VEPTR techniques appear to be living up to their promise.”

At 3 foot 8 inches, 66 pounds, Leta Moseley is a tiny teenager with a big personality. Seventeen years ago, her family embarked on a medical odyssey in search of a diagnosis for Leta, who has cognitive disabilities, speaks only a few words, and has lung disease and heart irregularities. A bad virus can land her in The Children’s Hospital of Philadelphia (CHOP) for several weeks, at times on a ventilator for breathing support. Yet, when she is healthy, Leta can take over a dance floor with her swirls and smiles.

CHOP medical geneticist and researcher Ian Krantz, MD, has been a tireless detective in his efforts to find out what genetic anomaly could be behind Leta’s constellation of symptoms. She had many characteristics in common with his patients with the rare multi-system disorder Cornelia de Lange Syndrome that Dr. Krantz has long studied. But her clinical features weren’t a perfect fit for this diagnosis, and genetic testing for Cornelia de Lange syndrome was negative. Dr. Krantz, Director of the Individualized Medical Genetics Center at CHOP, took Leta’s clinical history and photos all over the world with him to genetic conferences, in hopes of finding other children who shared Leta’s profile.

Over the past 10 years, Dr. Krantz and his team identified two other unrelated children (who live less than 200 miles away) with clinical features that seemed to match Leta’s. Using samples from all three children, his research team made the groundbreaking discovery “back home” in the genetics lab at CHOP. With the help of a breakthrough in sophisticated gene-sequencing technology that became available two years ago, they analyzed the protein-coding portions of DNA (exomes) and identified mutations in the AFF4 gene in Leta and the other two children. In genetic research, this is the equivalent of finding a needle in a haystack.

“This is a great example of how families and their doctors work together over many years to find answers and advance both science and the care of their children,” Dr. Krantz said. “Although it has been a long road to get to this point, it is really just the beginning, and we still need to work closely with the families to fully understand the significance of this discovery and how best to use this information to take better care of Leta and other children with this diagnosis.”

After years of mystery and misdiagnoses, Leta’s family finally has a name for her disorder — a new diagnosis called CHOPS syndrome. The acronym stands for the group of symptoms seen in the three affected children: Cognitive impairment and coarse facial features, Heart defects, Obesity, Pulmonary involvement, Short stature and skeletal dysplasia (abnormal bone development).

As this novel finding is disseminated in a Nature Genetics report, Dr. Krantz expects that CHOPS syndrome may be the answer for other parents around the world who have been on a hunt for their child’s complex, undiagnosed genetic disorder. They may find reassurance that CHOPS syndrome is a de novo condition — which means that it resulted from a new mutation arising in a single egg or sperm that went on to form the affected child but is not present in the patient’s parents — so it is unlikely to recur in any subsequent children.

“Ending the ‘diagnostic odyssey’ for families has a profound psychological effect, allowing for closure and an understanding of how all of these myriad clinical differences in their child are linked to a single underlying cause,” Dr. Krantz said. “It also ends a very expensive search for an answer often with many unnecessary diagnostic tests and blood draws. It allows us to find other children and adults with the same condition that in turn gives us a better understanding of the clinical issues and best options for management and to provide some idea of prognosis for families. We can more effectively counsel families about recurrence risk for themselves and family members. Most importantly, understanding the underlying molecular basis for the clinicalfindings in their children is the first step towards identifying targeted therapeutics in the future.”

In this interview, Leta’s mom, Lainey Moseley, described her family’s steadfast love for Leta along their unpredictable journey to the discovery of CHOPS Syndrome:

Q: Tell me about Leta; she seems to have quite a big personality.

A: It blows me away that so much is going on inside that little body of hers. It is so hard to really know what her potential is because we think she is brilliant and understands what is going on all the time. Yet, Leta has cognitive impairment, is nonverbal, has small stature, and she is pretty medically challenged with lung disease and pulmonary hypertension. Having said that, she does have a big personality given all her disabilities, and she endlessly amuses us with her antics. Life with Leta is chaotic and far from normal — the highs and lows are so extreme — but she gives us so much love in return. I cannot imagine our life without her.

Q: When you describe your search for a medical diagnosis for Leta as a “medical odyssey,” what does that mean to you?

A: Like everyone else, we really wanted to have a healthy child. We realized early on that Leta wasn’t hitting her milestones, and at one year old she was diagnosed with lung disease, but for 16 years no genetics doctors were able to give us a definitive genetics diagnosis. After many years, we gave up caring about a diagnosis; a label wasn’t going to alter the course of Leta’s life. But it was still unsettling not knowing how her disabilities were going to unfold. What was her lifespan going to be? Was the lung disease going to be a degenerative condition? We had no idea what her capacity was for learning or speaking. When you don’t have a diagnosis, you don’t know the end game or what to expect.

Q: How did you feel when Dr. Krantz told you that he had found this genetic glitch in Leta’s exome?

A: When Dr. Krantz called and told us that he had identified her gene mutation and that he actually had found two other kids like Leta, it was beyond exciting. I was so curious what these two other little kids, Liam and Nadira, would look like. Leta is so unique. It was hard to imagine that there were two other people in the world just like her. But the discovery also became important for other reasons. On an emotional level, when I found out her dad and I were not carriers of the AFF4 gene mutation, I realized that Leta’s medical issues were not my fault. All those years, I carried the burden that maybe I had done something wrong in my pregnancy that caused Leta’s genetic condition. A diagnosis let me off the hook of blaming myself. There’s nothing that I could have done differently to prevent it. This was just a random act of nature. That was a big turning point for me.

Q: So far, two other families are known to have the same genetic mutations as Leta. Why is it important for you to have this new connection?

A: It is important because we share a medical bond and now have a support group to compare notes about our kids, like what medicines are the doctors prescribing for their lung disease? What kind of communication devices do we each use? Does your child have the same hyperactive personality as mine? They are all so much alike, it is now almost like having triplets. I really am looking forward to getting to know Liam’s and Nadira’s families better. Having them in my life makes me feel so much less alone in my journey with Leta. Liam’s mom and I have become Facebook friends, and she was with me every step of the way praying for Leta when she was in the hospital last month on a ventilator.

Q: Overall, how has your experience been being part of Dr. Krantz’s research team?

A: The whole team has been phenomenal and so wonderful. They have been really supportive by keeping us informed about the ongoing AFF4 research. The genetics team is organizing a lunch next month so that our families can finally get together as a group. We’ve already learned that the research into the condition that Leta, Liam, and Nadira share could be groundbreaking in genetics and possibly lead to understanding roots of other genetic mutations. So that’s pretty exciting when it’s your child who is on the ground floor of that breakthrough. We’ve always thought that Leta is a superstar, but now she is a trailblazer in genetic research, giving other kids the chance to be born healthy.

The Children’s Hospital of Philadelphia Research Institute’s own Philip R. Johnson, MD was consulted for a number of articles about an exciting new HIV vaccine study. The study, published in Nature and led by the Scripps Research Institute’s Michael Farzan, PhD, describes the research team’s creation of a new molecule that prevents monkeys from being infected with simian/human immunodeficiency virus (SHIV).

“What Mike [Farzan] has done very ingeniously is to develop a molecule that attacks HIV in two different spots … [and] is able to neutralize most if not all strains of HIV,” said Dr. Johnson in Newsweek’s article about the project.

Dr. Farzan’s work builds on research by Dr. Johnson. In 2009 he published a study in Nature Medicinein which he worked with simian immunodeficiency virus (SIV) — which is closely related to HIV, and occurs in primates — to develop proteins that act like antibodies called immunoadhesins. These proteins, which Dr. Johnson and his team delivered via adeno-associated virus (AAV) vectors, were designed to prevent SIV from infecting cells. They found the immunoadhesins blocked SIV infection, protecting the primates used in the study.

When the Nature Medicine study was published, Steven Douglas, MD, medical director of CHOP’s Immunogenetics Laboratory, said, “Dr. Johnson’s groundbreaking research represents one of the biggest, most significant findings in the history of research at Children’s Hospital. This approach represents a paradigm shift in HIV research.”

Dr. Farzan’s recent paper, meanwhile, explores the effectiveness of a protein his team created, eCD4-Ig, at protecting against SHIV, a hybrid of HIV and SIV. The researchers — who include the University of Pennsylvania’s Beatrice H. Hahn, MD — found AAV-expressed eCD4-Ig protected macaques against SHIV “for more than 40 weeks” against “several infectious challenges.”

According to the CDC, more than 1.1 million Americans were living with HIV at the end of 2010, and approximately 35 million people around the world are living with the disease. An estimated 39 million people have died of HIV/AIDS since it was first recognized.

Dr. Johnson told the Wall Street Journalthat the molecule described by Dr. Farzan et al. “appears to be an extraordinarily potent molecule,” he said. “It’s further validating of the idea that we should be thinking in alternate terms about how to attack HIV vaccines. To me the nonhuman primate data are outstanding.”

And finally, speaking to Science, Dr. Johnson said eCD4-Ig “is a beautiful thing.”

For more information about Dr. Farzan’s SHIV study, see Nature. And to read an article about Dr. Johnson’s 2009 study that supports the new HIV work, check out the 2009 CHOP Research Annual Report.

As each child heard a series of tones, the MEG machine analyzed changing magnetic fields in the child’s brain, just as electroencephalography (EEG) detects electrical fields.

According to new research, children born with a DNA abnormality on chromosome 16 already linked to neurodevelopmental problems show measurable delays in processing sound and language. By strengthening the case that the deleted gene disrupts a key biological pathway, the study may lay the foundation for future medical treatments for specific subtypes of autism, along with cognitive and language disabilities.

Dr. Roberts led the study published recently in Cerebral Cortex, collaborating with a group from the University of California, San Francisco. The researchers examined children with copy number variants — either deletions or duplications­ of DNA — at the genetic site 16p11.2. Previous researchers had found that this location on chromosome 16 was associated with a subset of autism spectrum disorders (ASDs) and with developmental and language delays.

The researchers used magnetoencephalography (MEG), which detects magnetic fields in the brain, just as electroencephalography (EEG) detects electrical fields. As each child heard a series of tones, the MEG machine analyzed changing magnetic fields in the child’s brain, measuring an auditory processing delay called the M100 response latency.

The researchers analyzed 115 children: 43 with the 16p11.2 deletion, 23 with the 16p11.2 duplication, and 49 healthy controls. Only a fraction of the children had ASD diagnoses: 11 of the 43 with the deletion, and 2 of the 23 with the duplication.

In children with the deletion, the researchers found a significant delay: 23 milliseconds (ms), a figure that Dr. Roberts called “stunningly high” compared to the healthy children. There was no such delay among children with the duplication, who actually had a non-significant tendency to process sounds faster than the control subjects.

The 23-ms delay, about one-fortieth of a second, was twice as high as the 11-ms M100 delay that Dr. Roberts found in a 2010 magnetoencephalography study of children with ASDs.

While the 2010 study focused on children diagnosed with autism spectrum disorders, theCerebral Cortex study took a “genetics first” approach, analyzing children known to have genetic variants with or without ASD diagnoses. “We have approached the problem from both ends,” Dr. Roberts said. The previous study found a link between the brain and behavior, while this new study found a link between genetics and the brain.”

Although not all of the children with CNVs had autism, all of them had some neurological or learning disabilities, he noted. Because the severity of neurodevelopmental symptoms did not correlate with the length of the auditory processing delay, the M100 delay may not become a clear-cut diagnostic biomarker in neurological disorders, but it may be a clue to an important common pathway in neurobiology.

“We don’t yet know the significance of the 23-millisecond delay, but we have established its origin in genetics,” Dr. Roberts said. “It seems to be a proxy for something of biological significance.”

Further studies will investigate other genes previously implicated in autism spectrum disorders and other psychiatric disorders, to determine whether they also involve M100 response delays. “Our goal is to unify diverse genes along a few common pathways, some of which may be treatable with specific therapies,” said Dr. Roberts.

To read more about the Cerebral Cortex magnetoencephalography study, see a press release about the project.